2008 Grants - Zetterberg

2008 New Investigator Research Grant

The protein fragment beta-amyloid tends to accumulate into clumps within the Alzheimer brain. Beta-amyloid accumulation is thought to disrupt cell-to-cell communication and induce brain cell death.

Previous research has found that beta-amyloid may accumulate abnormally in the cerebrospinal fluid (CSF) surrounding the brain before aggregating in the brain itself. Henrik Zetterberg, M.D., Ph.D., and colleagues plan to study the biological mechanisms behind beta-amyloid accumulation in the CSF. For example, they expect to identify CSF proteins that inhibit beta-amyloid clearance. They then hope to determine how CSF amyloid clumps might lead to similar clumping in the brain, and which of these aggregates might prove most toxic to brain cells. Finally, the researchers will examine whether elderly people without dementia are protected from amyloid toxicity through 1) interactions of beta-amyloid with certain proteins or 2) chemical modifications of beta-amyloid itself.

For this effort, Dr. Zetterberg's team will study CSF samples from hundreds of people with and without Alzheimer's. The team will also conduct beta-amyloid studies with cultured cells and with rodents engineered to develop Alzheimer-like symptoms.

The results of this study could reveal new insights into how early Alzheimer's disease progresses. Such knowledge could lead to novel ways of diagnosing and treating the disease.